Biomarker patterns reflecting habitual food intake: the BARITONE sample and randomized controlled crossover trial protocol

Background Accurate assessment of dietary intake remains a major challenge in nutrition research and limits the ability to study diet–disease relationships. Most epidemiological studies rely on self-reported dietary data that are subject to measurement errors. Metabolomics has emerged as a promising approach for identifying objective biomarkers of dietary intake. However, validated biomarkers for current intake are still lacking for several key food groups, including different protein sources and vegetables, fruits, and berries. Objective The objective of this study is to identify and validate metabolomic biomarker patterns reflecting intake of these food groups as well as to identify groups of individuals with different responses to the trial foods. Methods The BARITONE project consists of two parts. First, individuals were recruited to a screening session. Second, from this larger sample, a subset of participants with high and low, respectively, intake of vegetables, fruit and berries were selected for participation in a randomized controlled three-period crossover dietary intervention trial. In the trial, participants consumed three dietary patterns differing in primary protein source (meat-based, fish-based, and plant-based) during three 1-week intervention periods separated by 1-week washout periods. Fasting blood and urine samples were collected at screening and pre- and post- each intervention week. Habitual dietary intake was assessed using 7-day weighed food diaries collected at screening and during both washout periods. Metabolomic profiling will be applied to identify biomarker patterns associated with the source of protein as well as changes in intake of vegetables, fruit and berries. These patterns of metabolites will be confirmed in the data on habitual dietary intake from the screening sample. Discussion This study provides a framework for identifying and validating metabolomic biomarker patterns of present dietary intake by combining controlled and observational data. The findings may contribute to improved dietary assessment and support future research on diet–health relationships. Clinical trial registration NCT07128940.